PhD defence F.G.C. (François) Blot

Neurons exist in many sizes, shapes and colors. This diversity has profound implications in regards to brain functions and pathologies. The works compile in this thesis aim to expand our conception of neuronal diversity. 
Continuums of transcriptomic variability among neurons with similar morphology define several neuronal subtypes. The Purkinje cell (PC) population, the principal neurons of the cerebellum, can be divided in subtypes which appear to have different sensitivities to pathological insult. We showed that preserved PCs maintain a proper execution of their behavioral output. Concluding that some neuronal pathways are deeply compartmentalized and degeneration of neighboring regions does not impact their functions. The molecular mechanisms behind the selective vulnerability of neuron subtypes remain largely unknown. We analyzed the metabolism of sphingolipids, complex lipids involved in cell apoptosis, in a mouse model presenting selective neurodegeneration of PC subtypes. We found that sphingolipids accumulate in the cerebellar region primarily affected by the neurodegeneration. Disrupting the sphingolipid metabolism via genetic mutation resulted in a neuroprotective effect on PCs. Thus, our data indicate that sphingolipid metabolism varies between neuronal subtypes and is determinant in the predisposition to neurodegeneration.
Variations in gene expression between subtypes reflect major differences in neuron intrinsic properties. We demonstrated that subtle nuances in Aldolase C protein expression profile among PC population correlates with variations in electrophysiological properties. The newly defined subtypes contrast essentially by their respecting projections to the vestibular formation that draw different compartmentalized networks.

Due to corona, the PhD defences do not take place publicly in the usual way in the Senate Hall or in the Professor Andries Querido Room. The candidates will defend their dissertation either in a small group or online.